Considerable evidence suggests that stem cells reside in the basal cell compartment of the epithelium of the adult prostate. Given the high proliferative potential of stem cells and the presence of undifferentiated cells in tumors, it is likely that diseases of abnormal growth of the prostate, including benign prostatic hyperplasia and prostate cancer, deriv. from and/or arc propagated by the stem cells. Despite this, the stem cells of the prostate are poorly characterized. Compelling evidence has led us to hypothesize that prostatic stem cells express the apoptosis-inhibiting protein bcl-2. To test this hypothesis, we aim to isolate fluorescing basal cells from the prostates of bcl-2/EGFP transgenic mice. We shall determine whether cells in this population have characteristics associated with stem cells. In addition, we shall use an inducible FLP recombinase- mediated strategy to track cell lineages deriving from bcl-2 expressing cells to determine whether these Cells arc multipotential progenitor cells that give rise to more differentiated cell types in the prostate. While it is beyond the budgetary constraints of this proposal, isolation of bcl-2 expressing cells will allow for a comparative analysis of cDNA prepared from the purified basal cell population with cDNAs from other cell populations. In this way, genes expressed specifically in prostatic basal cells will be identified. Further analysis of specific cDNA sequences will lead to the identification of genes that are expressed specifically in that subpopulation of basal cells that are stem cells. Ultimately, this work will identify attractive targets for therapeutic interventions for prostatic disease.